title: PAMAM G4 dendrimers affect the aggregation of α-synuclein.
abstract: α-Synuclein (ASN) aggregation plays a key role in neurodegenerative disorders including Parkinson's disease, and inhibition of fibril formation is a potential therapeutic strategy for these conditions. The aim of the present study was to investigate polyamidoamine (PAMAM) dendrimers (generations 4 and 3.5) as inhibitors of fibril formation in vitro by examining their interaction with ASN intrinsic tyrosine fluorescence. Furthermore, the effect of dendrimers on ASN aggregation was studied using circular dichroism (CD) spectroscopy and CD studies were complemented by a fluorescence assays using the dye thioflavin T (ThT). The PAMAM G4 dendrimer caused an increase in tyrosine residue fluorescence, and inhibited fibrillation of ASN; inhibited fibrillation was not observed with PAMAM G3.5 dendrimers.
authors.affiliation: Department of General Biophysics, University of Lodz, Lodz, Poland. milowska@biol.uni.lodz.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Milowska
authors.forename: Marta
authors.initials: M
authors.lastname: Malachowska
authors.forename: Teresa
authors.initials: T
authors.lastname: Gabryelak
mesh_terms: D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D051844:alpha-Synuclein; D014443:Tyrosine